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(Hypertension. 2000;36:734.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
From the Division of Nephrology (L.Z., G.B.), Dialysis and Hypertension, S. Raffaele Hospital, Milan, Italy; Prassis-Sigma Tau Research Institute (R.M., M.F., L.T., G.T.), Settimo Milanese, Milan, Italy; and The Wellcome Trust Centre for Human Genetics (M.-T.B.), University of Oxford, Oxford, UK.
Correspondence to Grazia Tripodi, PhD, Prassis-Sigma Tau Research Institute, via Forlanini 1, 20019 Settimo Milanese, Milano, Italy. E-mail pstbio{at}tin.it
AbstractIn a previous study, by
using a candidate gene approach, we detected in both Milan hypertensive
rats and humans a polymorphism in the
-adducin gene (ADD1) that
was associated with blood pressure and renal sodium handling. In the
present study, a genomewide search with 264 informative markers was
undertaken in 251 (Milan hypertensive strain x Milan normotensive
strain) F2 rats to further investigate the contribution of the adducin
gene family (Add1, Add2, and
Add3) and to identify novel quantitative trait loci
(QTLs) that affect blood pressure. The influence of 2 different methods
of blood pressure measurement, the intracarotid catheter and the
tail-cuff method, was also evaluated. We found evidence that QTLs
affected systolic blood pressure (SBP) measured at the carotid
(direct SBP) on rat chromosome 1 with a logarithm of the odds (LOD)
score peak of 3.3 on D1Rat121 and on rat chromosome 14 on
Add1 locus (LOD=3.2). A QTL for SBP measured at the tail
(indirect SBP) was found on rat chromosome 10 around D10Rat33
(LOD=5.0). All of these QTLs identified chromosomal regions not
detected in other rat studies and harbor genes
(Na+/H+ exchanger A3;
-adducin;
1B-adrenergic receptor) that may be involved in blood
pressure regulation. Therefore, these findings may be relevant to human
hypertension, also in consideration of the biochemical and
pathophysiological similarities between MHS and a
subgroup of patients of primary hypertension, which led to the
identification of
-adducin as a candidate gene in both species.
Key Words: genes rats, inbred strains hypertension, essential
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